Supplementary Material for: Tissue glue-based sealing patch for the in vivo prevention of iatrogenic prelabour preterm rupture of fetal membranes (iPPROM)

Introduction: One of the main concerns for all fetal surgeries is the risk of preterm delivery due to the preterm prelabor rupture of the fetal membranes (iPPROM). Clinical approaches to seal fetal membrane (FM) defects are missing due to the lack of appropriate strategies to apply sealing biomaterials at the defect site. Methods: Here, we test the performance of a previously developed strategy to seal FM defects with cyanoacrylate-based sealing patches in an ovine model up to 24 days after application. Results: Patches sealed tightly the fetoscopy-induced FM defects and remained firmly attached to the defect over 10 days. At 10 days after treatment 100% (13/13) of the patches were attached to the FMs, at 24 days after treatment 25% (1/4) of the patches placed in CO2 insufflation and 33% (1/3) in NaCl infusion remained. However, all successfully applied patches (20/24) led to a watertight sealing at 10 or 24 days after treatment. Histological analysis indicated that cyanoacrylates induced a moderate immune response and induced the disruption of the FM epithelium. Discussion/Conclusion: Together, these data show the feasibility of minimally-invasive sealing of FM defects by locally gathering tissue adhesive. Further development to combine this technology with refined tissue glues or healing-inducing materials holds great promise for future clinical translation.